Association of Factor V Leiden and Ischemic Stroke in Young Adults: A National Inpatient Sample Analysis

Association of Factor V Leiden and Ischemic Stroke in Young Adults: A National Inpatient Sample Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of Factor V Leiden and Ischemic Stroke in Young Adults: A National Inpatient Sample Analysis Jagkirat Singh, Ryan W Walters, Jack T Rausch, Ali Al-Salahat, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8191559/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Jan, 2026 Read the published version in Journal of Thrombosis and Thrombolysis → Version 1 posted You are reading this latest preprint version Abstract Background The association between Factor V Leiden (FVL) and ischemic stroke in young adults remains uncertain. We evaluated inpatient FVL prevalence and hospital outcomes among young adults with ischemic stroke in the United States. Methods Using the 2016–2022 National Inpatient Sample, we identified hospitalizations for patients aged 18–49 years with a primary diagnosis of ischemic stroke and a secondary diagnosis of FVL. FVL prevalence in stroke hospitalizations was compared with non-stroke hospitalizations. Among stroke hospitalizations, we examined discharge disposition, length of stay, and inflation-adjusted costs using survey-weighted models adjusted for demographics and comorbidities. Results Among 67.8 million hospitalizations of adults aged 18–49 years, 297,905 (0.44%) were for ischemic stroke. FVL prevalence was higher in stroke than non-stroke hospitalizations (0.85% vs 0.25%, p < 0.001) and rose modestly over time in stroke admissions (0.81% in 2016 to 0.95% in 2022). Stroke patients with FVL were younger, more often female and White, and had fewer traditional vascular risk factors. After adjustment, FVL was associated with longer length of stay (14.3% increase) and higher costs (16.5% increase), with greater effects in males and Black and Hispanic patients; discharge disposition was similar by FVL status. Conclusions FVL is more prevalent among young adults hospitalized with ischemic stroke, who did not have traditional stroke risk factors. These findings support a possible hypercoagulable mechanism in a subset of ischemic stroke patients and highlight the need for prospective studies to guide targeted screening and primary prevention strategies. Factor V Leiden Ischemic stroke Stroke in young National Inpatient Sample Hypercoagulable state Figures Figure 1 Figure 2 Introduction Stroke remains a major cause of death and disability worldwide, with ischemic stroke accounting for the majority of cases. In 2019 alone, approximately 5.87 million cases were reported in the United States, resulting in 110,000 deaths and 2.06 million disability-adjusted life years (DALYs) lost. [ 1 ] The incidence of ischemic stroke is highest among adults over the age of 50, [ 1 , 2 ] as advancing age allows for the accumulation of chronic cardiovascular changes that contribute to the condition’s most common etiologies. [ 3 ] Nonetheless, approximately 8% of ischemic strokes occur in younger adults, [ 1 ] in whom alternative etiologies such as hypercoagulable disorders are more prevalent. [ 4 ] One such disorder is Factor V Leiden (FVL). Factor V is a procoagulant protein synthesized in the liver. After a vascular insult, a cascade of protein interactions leads to the activation of factor V, facilitating the conversion of prothrombin to thrombin—an essential step in clot formation. [ 5 , 6 ] Once an adequate degree of clot formation has been achieved, activated protein C inhibits factor V via proteolytic cleavage of arginine residues, which downregulates thrombin generation. [ 7 , 8 ] Approximately 5% of Americans with European ancestry carry a missense mutation that substitutes glutamine for arginine at amino acid position 506. [ 9 ] The presence of glutamine renders factor V resistant to cleavage by activated protein C, leading to its persistence in circulation and thereby increased thrombin generation. This mutation was first described in 1994 at Leiden University Medical Center in the Netherlands and was termed Factor V Leiden. [ 10 ] FVL was quickly associated with up to an eightfold increase in venous thromboembolism; [ 11 – 13 ] however, its association with arterial events is more controversial. Some early studies noted an association with ischemic stroke, [ 14 – 16 ] yet large population-based studies to date have found no association in the general population [ 17 ] or even in young adults, [ 18 ] despite meta-analyses showing the strongest association in this age group. [ 19 – 21 ] Given these conflicting findings, our study aimed to investigate the association between FVL and ischemic stroke, as well as its effects on discharge outcomes, via a retrospective cohort study using the National Inpatient Sample. Methods Data Source Hospitalization data were abstracted from the 2016 to 2022 National Inpatient Sample (NIS), which was developed for the Healthcare Cost and Utilization Project (HCUP) in partnership with the Agency for Healthcare Research and Quality (AHRQ). The NIS is the largest publicly available inpatient database in the United States, approximating a 20% stratified sample of all discharges from U.S. community hospitals, excluding rehabilitation and long-term acute care hospitals. When weighted, the NIS approximates 35 million annual hospitalizations. [ 22 ] Hospitalization Cohort We abstracted all hospitalizations in which patients were aged 18 to 49 years and identified those with a primary discharge diagnosis of ischemic stroke (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM]: I63.xxx), further stratifying by the presence of a secondary FVL diagnosis (ICD-10-CM: D68.51). Although we originally planned to evaluate the presence of patent foramen ovale (PFO; ICD-10-CM: Q21.12), the ICD-10-CM code specific to PFO only went into effect in 2022Q4, precluding further evaluation. Prior to 2022Q4, a PFO diagnosis was subsumed within nonspecific coding for atrial septal defect (ICD-10-CM: Q21.1). Outcomes The primary outcome was overall and annual prevalence of FVL in an inpatient setting, estimated separately for hospitalizations due to ischemic stroke and hospitalizations due to other causes. Secondary outcomes among ischemic stroke hospitalizations included discharge disposition, length of stay, and hospital cost, which was inflation-adjusted to 2022 U.S. dollars. [ 23 ] Covariates For each hospitalization meeting inclusion criteria, we abstracted patient age, biological sex, race (White, Black, Hispanic, other race), hyperlipidemia (ICD-10-CM: E78.0–E78.5), and refined Elixhauser comorbidities for complicated and uncomplicated diabetes mellitus and hypertension. [ 24 ] Statistical Analysis Continuous variables are presented as medians with interquartile ranges, whereas categorical variables are presented as percentages. Overall and annual FVL prevalence estimates are presented with Wilson confidence intervals and compared using the Rao-Scott chi-square test. Annual trends in FVL prevalence were assessed using orthogonal polynomial contrasts. Unadjusted and adjusted lognormal models were estimated for length of stay and inflation-adjusted hospital cost, with adjusted models including the covariates defined above. The functional form of age was initially modeled using restricted cubic splines with knot points at the 5th, 35th, 65th, and 95th percentiles; retention of a nonlinear functional form was determined by the likelihood ratio test. Finally, we estimated two-way interactions between FVL and each covariate to determine whether the association between FVL and outcomes differed across covariate levels. All analyses were conducted using SAS v9.4, accounting for the NIS sampling design and discharge weights; two-tailed p < .05 indicated statistical significance. An asterisk denotes results that cannot be presented per the HCUP Nationwide Data Use Agreement due to < 11 unweighted hospitalizations. [ 25 ] Results Overall and Annual FVL Prevalence From 2016 to 2022, an estimated 67,823,156 hospitalizations included patients aged 18 to 49 years (95% CI: 67,110,600 to 68,545,711), of which 297,905 had a primary discharge diagnosis of ischemic stroke (0.44%, 95% CI: 0.43% to 0.45%). Among ischemic stroke hospitalizations, overall FVL prevalence was 0.85% (95% CI: 0.78% to 0.93%), which was statistically higher than FVL prevalence in hospitalizations due to other causes (0.25%, 95% CI: 0.24% to 0.25%; p < .001). Within ischemic stroke hospitalizations, an FVL diagnosis was associated with younger age, female sex, and White race, as well as lower prevalence of complicated diabetes mellitus, complicated hypertension, and hyperlipidemia. No statistically significant differences were observed in discharge disposition (Table 1 ). Annual Trend Analysis Annual trend analyses showed increasing linear trends in FVL prevalence (Fig. 1 ), with an 18.3% relative increase in ischemic stroke hospitalizations (0.81% in 2016 to 0.95% in 2022; p = .140) compared with a 36.5% relative increase in hospitalizations due to other causes (0.16% in 2016 to 0.22% in 2022; p < .001). Length of Stay Within ischemic stroke hospitalizations, overall length of stay was 4.6 days (95% CI: 4.6 to 4.7 days). After adjustment for demographic and clinical characteristics, FVL was associated with a 14.3% longer length of stay (95% CI: 9.3% to 19.5% longer; p < .001; Table 2 ). Longer adjusted lengths of stay were also associated with younger age, non-White race, complicated diabetes, and hypertension, whereas shorter adjusted lengths of stay were associated with uncomplicated diabetes and hyperlipidemia. The adjusted association between FVL and length of stay differed by biological sex (interaction p < .001), race (interaction p < .001), and uncomplicated hypertension (interaction p = .013). FVL was associated with 29.5% longer adjusted length of stay in males (95% CI: 19.5% to 40.4% longer; p < .001) compared with 4.9% longer adjusted length of stay in females (95% CI: 0.1% shorter to 10.1% longer; p = .057). FVL was associated with 14.0% longer adjusted length of stay in Whites (95% CI: 8.1% to 20.3% longer; p < .001), 22.3% longer adjusted length of stay in Blacks (95% CI: 7.7% to 38.9% longer; p = .002), and 23.1% longer adjusted length of stay in Hispanics (95% CI: 5.8% to 43.2% longer; p = .007). Finally, FVL was associated with 21.9% longer adjusted length of stay in those with uncomplicated hypertension (95% CI: 13.5% to 31.0% longer; p < .001) compared with 8.6% longer adjusted length of stay in those without uncomplicated hypertension (95% CI: 2.7% to 14.9% longer; p = .004). Inflation-adjusted Hospital Costs Within ischemic stroke hospitalizations, average inflation-adjusted hospital cost was $ 15,187 per hospitalization (95% CI: $ 15,044 to $ 15,331). After adjustment for demographic and clinical characteristics, FVL was associated with 16.5% higher costs (95% CI: 11.2% to 22.0% higher; p < .001; Table 3 ). Higher adjusted costs were associated with younger age, non-White race, and complicated hypertension, whereas lower adjusted costs were associated with diabetes mellitus and hyperlipidemia. The adjusted association between FVL and hospital cost differed by biological sex (interaction p < .001) and race (interaction p < .001). FVL was associated with 31.0% higher adjusted costs in males (95% CI: 20.7% to 42.1% higher; p < .001) compared with 7.5% higher adjusted costs in females (95% CI: 2.1% to 13.1% higher; p = .006). FVL was associated with 13.5% higher adjusted costs in Whites (95% CI: 7.5% to 19.8% higher; p < .001) and even larger increases in Blacks (31.8% higher; 95% CI: 15.4% to 50.5% higher; p < .001) and Hispanics (53.3% higher; 95% CI: 34.1% to 75.1% higher; p < .001). Discussion Although the association between FVL and venous thromboembolism is well established, [ 13 ] evidence regarding its association with ischemic stroke remains conflicting. Several meta-analyses have demonstrated a correlation, [ 16 , 19 , 20 , 26 ] particularly in young females, [ 16 ] but large individual studies have not found similar results. [ 17 , 18 ] Our aim in this study was to investigate the association between FVL and ischemic stroke and its effects on discharge outcomes using the National Inpatient Sample. We found that FVL was present in 0.9% of ischemic stroke hospitalizations compared with 0.2% of non-stroke hospitalizations, suggesting a higher prevalence among stroke patients. Stroke patients with FVL were younger, more likely to be female, and more likely to be White. They also had fewer traditional stroke risk factors, including hyperlipidemia, complicated hypertension, and complicated diabetes. FVL-positive patients had longer hospital stays and higher costs, with these effects more pronounced in younger patients. These findings differ from some national studies but align with prior meta-analyses. The demographic and clinical profile observed among FVL-positive stroke patients supports the hypothesis that this mutation may contribute to stroke through non-atherosclerotic mechanisms. Traditional vascular risk factors were less prevalent in this group, suggesting that hypercoagulability may play a larger role than atherosclerotic disease. FVL causes resistance to activated protein C, resulting in sustained thrombin generation and a prothrombotic state. In the context of stroke, this may increase the risk of in situ arterial thrombosis or paradoxical embolism through a patent foramen ovale (PFO). [ 27 ] The younger age and female predominance observed in our cohort are consistent with known epidemiologic patterns of FVL, [ 28 ] which is more common in individuals of European ancestry and may interact with hormonal factors such as oral contraceptive use or pregnancy to augment thrombotic risk, as shown in venous thromboembolism studies. [ 29 – 31 ] Clinically, these findings suggest that FVL may be relevant in the evaluation of ischemic stroke in younger adults, particularly when traditional vascular risk factors are absent or the etiology is cryptogenic. While routine screening for FVL in all stroke patients is not currently recommended, [ 32 ] targeted testing in select cases—such as young, female, or White patients without other clear risk factors—may help refine secondary prevention strategies. Identification of FVL may also inform counseling regarding estrogen-containing contraceptives, pregnancy management, and consideration of anticoagulation in patients with concurrent venous thromboembolism risk. This study has several strengths, including use of a large, nationally representative database that enabled assessment of a rare genetic variant in a broad inpatient population. However, limitations should be noted. The retrospective cross-sectional design precludes causal inference, and reliance on ICD coding introduces potential misclassification. The low prevalence of FVL limits detailed subgroup analyses, and findings may not generalize to outpatient or subclinical stroke populations. Additionally, the NIS does not provide information on FVL zygosity (heterozygous vs homozygous) or PFO status, which limits mechanistic interpretation. Conclusion This study demonstrates that Factor V Leiden is more prevalent among patients hospitalized with ischemic stroke than among those without stroke, particularly in younger, female, and White individuals with fewer traditional vascular risk factors. These findings support a possible hypercoagulable mechanism in a subset of ischemic stroke patients and highlight the need for prospective studies with patient-level genetic and clinical data to better define the role of FVL in arterial thrombosis and to guide targeted screening and prevention strategies. Declarations Data availability statement The data that support the findings of this study were derived from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality (AHRQ), 2016–2022 . These data are not publicly available because they are distributed under the HCUP Nationwide Data Use Agreement (DUA) and require purchase and completion of HCUP training. Researchers may obtain the NIS directly from HCUP at the HCUP Central Distributor (dataset title: National Inpatient Sample (NIS), 2016–2022 ; repository: HCUP Central Distributor ; persistent identifier: HCUP NIS product ). The analytic methods and derived summary results are provided in this article and its Supplementary Information; additional programming code is available from the corresponding author upon reasonable request. Competing inteterest and Funding statement The authors have no competing interests to declare that are relevant to the content of this article and have received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Ethics approval statement This study was reviewed and approved by the Creighton University Institutional Review Board (IRB). The study used de-identified, publicly available National Inpatient Sample (NIS) data and was determined to be exempt from human subjects research requirements; therefore, informed consent was waived. (IRB approval/exemption number: [2044691-01]; date of determination: [6 th October, 2025). Informed consent statement Informed consent was not required for this study because it involved analysis of de-identified, publicly available data from the National Inpatient Sample. The Creighton University Institutional Review Board determined the study to be exempt and waived the requirement for informed consent. Consent to participate statement Consent to participate was not required because this study analyzed de-identified, publicly available National Inpatient Sample data. The Creighton University Institutional Review Board approved the study and waived the requirement for informed consent. Consent to publish statement Consent to publish was not required because this study used de-identified, publicly available National Inpatient Sample data and contains no individually identifiable information. The Creighton University Institutional Review Board approved the study and waived the requirement for consent to publish. References Renedo D, Acosta JN, Leasure AC et al (2024) Burden of ischemic and hemorrhagic stroke across the US from 1990 to 2019. JAMA Neurol 81(4):394–404. 10.1001/jamaneurol.2024.0190 Koton S, Schneider ALC, Rosamond WD et al (2014) Stroke incidence and mortality trends in US communities, 1987 to 2011. JAMA 312(3):259–268. 10.1001/jama.2014.7692 Ornello R, Degan D, Tiseo C et al (2018) Distribution and temporal trends from 1993 to 2015 of ischemic stroke subtypes: a systematic review and meta-analysis. 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Demographic and clinical characteristics for hospitalizations due to ischemic stroke stratified by FVL status Overall Factor V Leiden No Yes P Hospitalizations, count Unweighted 59,581 59,072 (99.1) 509 (0.9) - Weighted 297,905 295,360 (99.1) 2,545 (0.9) - Age, median [IQR] 43 [38–46] 43 [38–46] 41 [35–45] < .001 Biological Sex, % Male 53.4 53.5 40.1 < .001 Female 46.6 46.5 59.9 Race, % White 50.7 50.5 73.2 < .001 Black 28.1 28.2 15.0 Hispanic 13.7 13.7 5.7 Other 7.5 7.5 6.1 Diabetes, % Uncomplicated 11.7 11.8 9.8 0.178 Complicated 20.0 20.1 13.6 < .001 Hypertension, % Uncomplicated 47.4 47.4 44.4 0.178 Complicated 20.8 20.8 15.9 0.008 Hyperlipidemia, % 43.9 43.9 38.9 0.023 Discharge Disposition, % Routine 60.2 60.3 57.7 0.147 Transfer to Acute Care 3.6 3.6 2.6 SNF/Rehab 22.0 22.0 24.0 Home Healthcare 8.6 8.6 10.2 Left Against Medical Advice 3.4 3.4 4.3 In-hospital Mortality 2.0 2.2 * Note. Data presented as count, median [interquartile range], or percent Table 2 Unadjusted and adjusted model results for length of stay Unadjusted Adjusted Days Ratio (95% CI) p Ratio (95% CI) p Overall 4.6 - - - - Factor V Leiden Yes 5.1 1.11 (1.03–1.18) 0.005 1.14 (1.09–1.20) < .001 No 4.6 Reference Reference Age (per 10 years older) Figure 2 0.98 (0.97–0.99) < .001 0.96 (0.96–0.97) < .001 Biological Sex Female 4.6 0.99 (0.98–0.99) 0.044 0.99 (0.98–1.01) 0.180 Male 4.7 Reference Reference Race Black 5.1 1.17 (1.16–1.18) < .001 1.11 (1.11–1.12) < .001 Hispanic 4.8 1.09 (1.08–1.10) < .001 1.07 (1.06–1.08) < .001 Other 4.7 1.09 (1.07–1.10) < .001 1.07 (1.05–1.08) < .001 White 4.4 Reference Reference Diabetes - Uncomplicated Yes 4.4 0.93 (0.92–0.95) < .001 0.97 (0.96 − 0.78) < .001 No 4.7 Reference Reference Diabetes - Complicated Yes 5.2 1.16 (1.15–1.18) < .001 1.10 (1.09–1.11) < .001 No 4.5 Reference Reference Hypertension - Uncomplicated Yes 4.4 0.91 (0.90–0.92) < .001 1.02 (1.01–1.03) < .001 No 4.9 Reference Reference Hypertension - Complicated Yes 5.6 1.31 (1.29–1.33) < .001 1.29 (1.28–1.30) < .001 No 4.4 Reference Reference Hyperlipidemia Yes 4.6 0.97 (0.96–0.98) < .001 0.94 (0.94–0.95) < .001 No 4.7 Reference Reference Note . Ratios are interpreted relative to the reference group. For age, the reference group is 10-years younger age; for categorical variables the reference group is indicated. Ratios greater than 1 indicate longer lengths of stay relative to the reference group. Table 3 Unadjusted and adjusted model results for inflation-adjusted hospital cost Unadjusted Adjusted 2022 US $ Ratio (95% CI) p Ratio (95% CI) p Overall 15,187 - - - - Factor V Leiden Yes 17,172 1.13 (1.05–1.22) 0.001 1.16 (1.11–1.22) < .001 No 15,171 Reference Reference Age (per 10 years older) Figure 2 0.91 (0.90–0.91) < .001 0.93 (0.92–0.93) < .001 Biological Sex Female 15,174 1.00 (0.99–1.01) 0.819 1.00 (0.99–1.01) 0.202 Male 15,196 Reference Reference Race Black 15,403 1.07 (1.06–1.08) < .001 1.06 (1.0-1.07) < .001 Hispanic 16,836 1.17 (1.16–1.19) < .001 1.17 (1.16–1.18) < .001 Other 17,344 1.21 (1.19–1.23) < .001 1.21 (1.19–1.23) < .001 White 14,340 Reference Reference Diabetes - Uncomplicated Yes 13,596 0.88 (0.87–0.90) < .001 0.92 (0.90–0.93) < .001 No 15,419 Reference Reference Diabetes - Complicated Yes 15,256 1.01 (0.99–1.02) 0.493 0.99 (0.98–0.99) 0.020 No 15,169 Reference Reference Hypertension - Uncomplicated Yes 14,107 0.97 (0.86–0.88) < .001 0.95 (0.94–0.96) < .001 No 16,231 Reference Reference Hypertension - Complicated Yes 16,903 1.14 (1.13–1.16) < .001 1.12 (1.11–1.14) < .001 No 14,765 Reference Reference Hyperlipidemia Yes 14,369 0.91 (0.89–0.92) < .001 0.93 (0.93–0.94) < .001 No 15,858 Reference Reference Note . Ratios are interpreted relative to the reference group. For age, the reference group is 10-years younger age; for categorical variables the reference group is indicated. Ratios greater than 1 indicate higher hospital costs relative to the reference group. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Jan, 2026 Read the published version in Journal of Thrombosis and Thrombolysis → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Singh","email":"data:image/png;base64,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","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Jagkirat","middleName":"","lastName":"Singh","suffix":""},{"id":550227603,"identity":"2596ac3f-0c26-449a-b51c-cb84a354cdfb","order_by":1,"name":"Ryan W Walters","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ryan","middleName":"W","lastName":"Walters","suffix":""},{"id":550227604,"identity":"6e0796c3-ab8f-41d6-87c7-06f99cadf9eb","order_by":2,"name":"Jack T Rausch","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Jack","middleName":"T","lastName":"Rausch","suffix":""},{"id":550227605,"identity":"cb8d0a96-b4a8-4044-87ef-d95fd18537e0","order_by":3,"name":"Ali Al-Salahat","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"","lastName":"Al-Salahat","suffix":""},{"id":550227606,"identity":"414fd1f6-0a19-4a88-8b56-f2ea60f7e55c","order_by":4,"name":"Evanthia Bernitsas","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Evanthia","middleName":"","lastName":"Bernitsas","suffix":""}],"badges":[],"createdAt":"2025-11-24 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08:23:03","extension":"xml","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":108881,"visible":true,"origin":"","legend":"","description":"","filename":"60f84272ebc74f14bb000f182ea2e4e31structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8191559/v1/a2775bd6a393c331137adcb4.xml"},{"id":97126063,"identity":"2445da95-56fa-4af0-abab-932617b5ef60","added_by":"auto","created_at":"2025-12-01 08:23:03","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":117039,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8191559/v1/bd9c590a27b78d2b5a0f1bd3.html"},{"id":97126058,"identity":"a32fef3c-a952-4aff-8692-d04d6f74cf40","added_by":"auto","created_at":"2025-12-01 08:23:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36611,"visible":true,"origin":"","legend":"\u003cp\u003eAnnual trends in FVL prevalence for hospitalization due to ischemic stroke and hospitalizations due to other causes. Error bars represent 95% confidence intervals.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8191559/v1/154450c980205217779f801c.png"},{"id":97126056,"identity":"77855b17-6753-431c-8e0f-8bf069c13e5e","added_by":"auto","created_at":"2025-12-01 08:23:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":69454,"visible":true,"origin":"","legend":"\u003cp\u003eUnadjusted association between age and length of stay (top) and inflation-adjusted hospital cost (bottom). The thick blue line indicates the average length of stay or hospital cost for a given age with shaded areas representing 95% confidence intervals.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8191559/v1/3053fd2b1823cd47b5966ec0.png"},{"id":100615677,"identity":"a9b07910-0471-4dbc-b591-880e521905c2","added_by":"auto","created_at":"2026-01-19 17:35:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1027650,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8191559/v1/08cb2a38-c170-4172-8af5-b619c812bb66.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of Factor V Leiden and Ischemic Stroke in Young Adults: A National Inpatient Sample Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eStroke remains a major cause of death and disability worldwide, with ischemic stroke accounting for the majority of cases. In 2019 alone, approximately 5.87\u0026nbsp;million cases were reported in the United States, resulting in 110,000 deaths and 2.06\u0026nbsp;million disability-adjusted life years (DALYs) lost. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The incidence of ischemic stroke is highest among adults over the age of 50, [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] as advancing age allows for the accumulation of chronic cardiovascular changes that contribute to the condition\u0026rsquo;s most common etiologies. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Nonetheless, approximately 8% of ischemic strokes occur in younger adults, [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] in whom alternative etiologies such as hypercoagulable disorders are more prevalent. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] One such disorder is Factor V Leiden (FVL).\u003c/p\u003e\u003cp\u003eFactor V is a procoagulant protein synthesized in the liver. After a vascular insult, a cascade of protein interactions leads to the activation of factor V, facilitating the conversion of prothrombin to thrombin\u0026mdash;an essential step in clot formation. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Once an adequate degree of clot formation has been achieved, activated protein C inhibits factor V via proteolytic cleavage of arginine residues, which downregulates thrombin generation. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Approximately 5% of Americans with European ancestry carry a missense mutation that substitutes glutamine for arginine at amino acid position 506. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] The presence of glutamine renders factor V resistant to cleavage by activated protein C, leading to its persistence in circulation and thereby increased thrombin generation. This mutation was first described in 1994 at Leiden University Medical Center in the Netherlands and was termed Factor V Leiden. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eFVL was quickly associated with up to an eightfold increase in venous thromboembolism; [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] however, its association with arterial events is more controversial. Some early studies noted an association with ischemic stroke, [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] yet large population-based studies to date have found no association in the general population [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] or even in young adults, [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] despite meta-analyses showing the strongest association in this age group. [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Given these conflicting findings, our study aimed to investigate the association between FVL and ischemic stroke, as well as its effects on discharge outcomes, via a retrospective cohort study using the National Inpatient Sample.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eData Source\u003c/p\u003e\u003cp\u003eHospitalization data were abstracted from the 2016 to 2022 National Inpatient Sample (NIS), which was developed for the Healthcare Cost and Utilization Project (HCUP) in partnership with the Agency for Healthcare Research and Quality (AHRQ). The NIS is the largest publicly available inpatient database in the United States, approximating a 20% stratified sample of all discharges from U.S. community hospitals, excluding rehabilitation and long-term acute care hospitals. When weighted, the NIS approximates 35\u0026nbsp;million annual hospitalizations. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eHospitalization Cohort\u003c/p\u003e\u003cp\u003eWe abstracted all hospitalizations in which patients were aged 18 to 49 years and identified those with a primary discharge diagnosis of ischemic stroke (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM]: I63.xxx), further stratifying by the presence of a secondary FVL diagnosis (ICD-10-CM: D68.51). Although we originally planned to evaluate the presence of patent foramen ovale (PFO; ICD-10-CM: Q21.12), the ICD-10-CM code specific to PFO only went into effect in 2022Q4, precluding further evaluation. Prior to 2022Q4, a PFO diagnosis was subsumed within nonspecific coding for atrial septal defect (ICD-10-CM: Q21.1).\u003c/p\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003cp\u003eThe primary outcome was overall and annual prevalence of FVL in an inpatient setting, estimated separately for hospitalizations due to ischemic stroke and hospitalizations due to other causes. Secondary outcomes among ischemic stroke hospitalizations included discharge disposition, length of stay, and hospital cost, which was inflation-adjusted to 2022 U.S. dollars. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eCovariates\u003c/p\u003e\u003cp\u003eFor each hospitalization meeting inclusion criteria, we abstracted patient age, biological sex, race (White, Black, Hispanic, other race), hyperlipidemia (ICD-10-CM: E78.0\u0026ndash;E78.5), and refined Elixhauser comorbidities for complicated and uncomplicated diabetes mellitus and hypertension. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eContinuous variables are presented as medians with interquartile ranges, whereas categorical variables are presented as percentages. Overall and annual FVL prevalence estimates are presented with Wilson confidence intervals and compared using the Rao-Scott chi-square test. Annual trends in FVL prevalence were assessed using orthogonal polynomial contrasts. Unadjusted and adjusted lognormal models were estimated for length of stay and inflation-adjusted hospital cost, with adjusted models including the covariates defined above. The functional form of age was initially modeled using restricted cubic splines with knot points at the 5th, 35th, 65th, and 95th percentiles; retention of a nonlinear functional form was determined by the likelihood ratio test. Finally, we estimated two-way interactions between FVL and each covariate to determine whether the association between FVL and outcomes differed across covariate levels. All analyses were conducted using SAS v9.4, accounting for the NIS sampling design and discharge weights; two-tailed p\u0026thinsp;\u0026lt;\u0026thinsp;.05 indicated statistical significance. An asterisk denotes results that cannot be presented per the HCUP Nationwide Data Use Agreement due to \u0026lt;\u0026thinsp;11 unweighted hospitalizations. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOverall and Annual FVL Prevalence\u003c/p\u003e\u003cp\u003eFrom 2016 to 2022, an estimated 67,823,156 hospitalizations included patients aged 18 to 49 years (95% CI: 67,110,600 to 68,545,711), of which 297,905 had a primary discharge diagnosis of ischemic stroke (0.44%, 95% CI: 0.43% to 0.45%). Among ischemic stroke hospitalizations, overall FVL prevalence was 0.85% (95% CI: 0.78% to 0.93%), which was statistically higher than FVL prevalence in hospitalizations due to other causes (0.25%, 95% CI: 0.24% to 0.25%; p\u0026thinsp;\u0026lt;\u0026thinsp;.001). Within ischemic stroke hospitalizations, an FVL diagnosis was associated with younger age, female sex, and White race, as well as lower prevalence of complicated diabetes mellitus, complicated hypertension, and hyperlipidemia. No statistically significant differences were observed in discharge disposition (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAnnual Trend Analysis\u003c/p\u003e\u003cp\u003eAnnual trend analyses showed increasing linear trends in FVL prevalence (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), with an 18.3% relative increase in ischemic stroke hospitalizations (0.81% in 2016 to 0.95% in 2022; p\u0026thinsp;=\u0026thinsp;.140) compared with a 36.5% relative increase in hospitalizations due to other causes (0.16% in 2016 to 0.22% in 2022; p\u0026thinsp;\u0026lt;\u0026thinsp;.001).\u003c/p\u003e\u003cp\u003eLength of Stay\u003c/p\u003e\u003cp\u003eWithin ischemic stroke hospitalizations, overall length of stay was 4.6 days (95% CI: 4.6 to 4.7 days). After adjustment for demographic and clinical characteristics, FVL was associated with a 14.3% longer length of stay (95% CI: 9.3% to 19.5% longer; p\u0026thinsp;\u0026lt;\u0026thinsp;.001; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Longer adjusted lengths of stay were also associated with younger age, non-White race, complicated diabetes, and hypertension, whereas shorter adjusted lengths of stay were associated with uncomplicated diabetes and hyperlipidemia.\u003c/p\u003e\u003cp\u003eThe adjusted association between FVL and length of stay differed by biological sex (interaction p\u0026thinsp;\u0026lt;\u0026thinsp;.001), race (interaction p\u0026thinsp;\u0026lt;\u0026thinsp;.001), and uncomplicated hypertension (interaction p\u0026thinsp;=\u0026thinsp;.013). FVL was associated with 29.5% longer adjusted length of stay in males (95% CI: 19.5% to 40.4% longer; p\u0026thinsp;\u0026lt;\u0026thinsp;.001) compared with 4.9% longer adjusted length of stay in females (95% CI: 0.1% shorter to 10.1% longer; p\u0026thinsp;=\u0026thinsp;.057). FVL was associated with 14.0% longer adjusted length of stay in Whites (95% CI: 8.1% to 20.3% longer; p\u0026thinsp;\u0026lt;\u0026thinsp;.001), 22.3% longer adjusted length of stay in Blacks (95% CI: 7.7% to 38.9% longer; p\u0026thinsp;=\u0026thinsp;.002), and 23.1% longer adjusted length of stay in Hispanics (95% CI: 5.8% to 43.2% longer; p\u0026thinsp;=\u0026thinsp;.007). Finally, FVL was associated with 21.9% longer adjusted length of stay in those with uncomplicated hypertension (95% CI: 13.5% to 31.0% longer; p\u0026thinsp;\u0026lt;\u0026thinsp;.001) compared with 8.6% longer adjusted length of stay in those without uncomplicated hypertension (95% CI: 2.7% to 14.9% longer; p\u0026thinsp;=\u0026thinsp;.004).\u003c/p\u003e\u003cp\u003eInflation-adjusted Hospital Costs\u003c/p\u003e\u003cp\u003eWithin ischemic stroke hospitalizations, average inflation-adjusted hospital cost was \u003cspan\u003e$\u003c/span\u003e15,187 per hospitalization (95% CI: \u003cspan\u003e$\u003c/span\u003e15,044 to \u003cspan\u003e$\u003c/span\u003e15,331). After adjustment for demographic and clinical characteristics, FVL was associated with 16.5% higher costs (95% CI: 11.2% to 22.0% higher; p\u0026thinsp;\u0026lt;\u0026thinsp;.001; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Higher adjusted costs were associated with younger age, non-White race, and complicated hypertension, whereas lower adjusted costs were associated with diabetes mellitus and hyperlipidemia.\u003c/p\u003e\u003cp\u003eThe adjusted association between FVL and hospital cost differed by biological sex (interaction p\u0026thinsp;\u0026lt;\u0026thinsp;.001) and race (interaction p\u0026thinsp;\u0026lt;\u0026thinsp;.001). FVL was associated with 31.0% higher adjusted costs in males (95% CI: 20.7% to 42.1% higher; p\u0026thinsp;\u0026lt;\u0026thinsp;.001) compared with 7.5% higher adjusted costs in females (95% CI: 2.1% to 13.1% higher; p\u0026thinsp;=\u0026thinsp;.006). FVL was associated with 13.5% higher adjusted costs in Whites (95% CI: 7.5% to 19.8% higher; p\u0026thinsp;\u0026lt;\u0026thinsp;.001) and even larger increases in Blacks (31.8% higher; 95% CI: 15.4% to 50.5% higher; p\u0026thinsp;\u0026lt;\u0026thinsp;.001) and Hispanics (53.3% higher; 95% CI: 34.1% to 75.1% higher; p\u0026thinsp;\u0026lt;\u0026thinsp;.001).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAlthough the association between FVL and venous thromboembolism is well established, [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] evidence regarding its association with ischemic stroke remains conflicting. Several meta-analyses have demonstrated a correlation, [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] particularly in young females, [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] but large individual studies have not found similar results. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] Our aim in this study was to investigate the association between FVL and ischemic stroke and its effects on discharge outcomes using the National Inpatient Sample.\u003c/p\u003e\u003cp\u003eWe found that FVL was present in 0.9% of ischemic stroke hospitalizations compared with 0.2% of non-stroke hospitalizations, suggesting a higher prevalence among stroke patients. Stroke patients with FVL were younger, more likely to be female, and more likely to be White. They also had fewer traditional stroke risk factors, including hyperlipidemia, complicated hypertension, and complicated diabetes. FVL-positive patients had longer hospital stays and higher costs, with these effects more pronounced in younger patients. These findings differ from some national studies but align with prior meta-analyses.\u003c/p\u003e\u003cp\u003eThe demographic and clinical profile observed among FVL-positive stroke patients supports the hypothesis that this mutation may contribute to stroke through non-atherosclerotic mechanisms. Traditional vascular risk factors were less prevalent in this group, suggesting that hypercoagulability may play a larger role than atherosclerotic disease. FVL causes resistance to activated protein C, resulting in sustained thrombin generation and a prothrombotic state. In the context of stroke, this may increase the risk of in situ arterial thrombosis or paradoxical embolism through a patent foramen ovale (PFO). [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] The younger age and female predominance observed in our cohort are consistent with known epidemiologic patterns of FVL, [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] which is more common in individuals of European ancestry and may interact with hormonal factors such as oral contraceptive use or pregnancy to augment thrombotic risk, as shown in venous thromboembolism studies. [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eClinically, these findings suggest that FVL may be relevant in the evaluation of ischemic stroke in younger adults, particularly when traditional vascular risk factors are absent or the etiology is cryptogenic. While routine screening for FVL in all stroke patients is not currently recommended, [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] targeted testing in select cases\u0026mdash;such as young, female, or White patients without other clear risk factors\u0026mdash;may help refine secondary prevention strategies. Identification of FVL may also inform counseling regarding estrogen-containing contraceptives, pregnancy management, and consideration of anticoagulation in patients with concurrent venous thromboembolism risk.\u003c/p\u003e\u003cp\u003eThis study has several strengths, including use of a large, nationally representative database that enabled assessment of a rare genetic variant in a broad inpatient population. However, limitations should be noted. The retrospective cross-sectional design precludes causal inference, and reliance on ICD coding introduces potential misclassification. The low prevalence of FVL limits detailed subgroup analyses, and findings may not generalize to outpatient or subclinical stroke populations. Additionally, the NIS does not provide information on FVL zygosity (heterozygous vs homozygous) or PFO status, which limits mechanistic interpretation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrates that Factor V Leiden is more prevalent among patients hospitalized with ischemic stroke than among those without stroke, particularly in younger, female, and White individuals with fewer traditional vascular risk factors. These findings support a possible hypercoagulable mechanism in a subset of ischemic stroke patients and highlight the need for prospective studies with patient-level genetic and clinical data to better define the role of FVL in arterial thrombosis and to guide targeted screening and prevention strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study were derived from the\u003cstrong\u003eNational Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality (AHRQ), 2016\u0026ndash;2022\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eThese data are\u003cstrong\u003enot publicly available\u003c/strong\u003ebecause they are distributed under the\u003cstrong\u003eHCUP Nationwide Data Use Agreement (DUA)\u003c/strong\u003e and require purchase and completion of HCUP training. Researchers may obtain the NIS directly from HCUP at the HCUP Central Distributor (dataset title:\u0026nbsp;\u003cem\u003eNational Inpatient Sample (NIS), 2016\u0026ndash;2022\u003c/em\u003e; repository:\u0026nbsp;\u003cem\u003eHCUP Central Distributor\u003c/em\u003e; persistent identifier:\u0026nbsp;\u003cem\u003eHCUP NIS product\u003c/em\u003e). The analytic methods and derived summary results are provided in this article and its Supplementary Information; additional programming code is available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting inteterest and Funding statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no competing interests to declare that are relevant to the content of this article and have \u0026nbsp;\u003cstrong\u003ereceived no specific grant\u003c/strong\u003e from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was reviewed and approved by the Creighton University Institutional Review Board (IRB). The study used de-identified, publicly available National Inpatient Sample (NIS) data and was determined to be exempt from human subjects research requirements; therefore, informed consent was waived. \u003cem\u003e(IRB approval/exemption number: [2044691-01]; date of determination: [6\u003csup\u003eth\u003c/sup\u003e October, 2025).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was not required for this study because it involved analysis of de-identified, publicly available data from the National Inpatient Sample. The Creighton University Institutional Review Board determined the study to be exempt and waived the requirement for informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent to participate was not required because this study analyzed de-identified, publicly available National Inpatient Sample data. The Creighton University Institutional Review Board approved the study and waived the requirement for informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent to publish was not required because this study used de-identified, publicly available National Inpatient Sample data and contains no individually identifiable information. The Creighton University Institutional Review Board approved the study and waived the requirement for consent to publish.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRenedo D, Acosta JN, Leasure AC et al (2024) Burden of ischemic and hemorrhagic stroke across the US from 1990 to 2019. JAMA Neurol 81(4):394\u0026ndash;404. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaneurol.2024.0190\u003c/span\u003e\u003cspan address=\"10.1001/jamaneurol.2024.0190\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoton S, Schneider ALC, Rosamond WD et al (2014) Stroke incidence and mortality trends in US communities, 1987 to 2011. 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Contraception 110943. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.contraception.2025.110943\u003c/span\u003e\u003cspan address=\"10.1016/j.contraception.2025.110943\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStegeman BH, De Bastos M, Rosendaal FR et al (2013) Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ 347:f5298. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.f5298\u003c/span\u003e\u003cspan address=\"10.1136/bmj.f5298\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGrody WW, Griffin JH, Taylor AK, Korf BR, Heit JA (2001) American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med 3(2):139\u0026ndash;148. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/00125817-200103000-00009\u003c/span\u003e\u003cspan address=\"10.1097/00125817-200103000-00009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\"\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Demographic and clinical characteristics for hospitalizations due to ischemic stroke stratified by FVL status\u003c/div\u003e\n \u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eOverall\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFactor V Leiden\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHospitalizations, count\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUnweighted\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e59,581\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e59,072 (99.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e509 (0.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWeighted\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e297,905\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e295,360 (99.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2,545 (0.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge, median [IQR]\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e43 [38\u0026ndash;46]\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e43 [38\u0026ndash;46]\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e41 [35\u0026ndash;45]\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBiological Sex, %\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e53.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e53.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e40.1\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e46.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e46.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e59.9\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRace, %\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWhite\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e50.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e50.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e73.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBlack\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e28.1\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e28.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15.0\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHispanic\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e5.7\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eOther\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6.1\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDiabetes, %\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUncomplicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e11.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e11.8\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e9.8\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.178\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eComplicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e20.0\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e20.1\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHypertension, %\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUncomplicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e47.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e47.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e44.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.178\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eComplicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e20.8\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e20.8\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15.9\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.008\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHyperlipidemia, %\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e43.9\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e43.9\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e38.9\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.023\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDischarge Disposition, %\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRoutine\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e60.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e60.3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e57.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"6\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.147\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eTransfer to Acute Care\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2.6\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eSNF/Rehab\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e22.0\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e22.0\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e24.0\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHome Healthcare\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e8.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e8.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10.2\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLeft Against Medical Advice\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.3\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eIn-hospital Mortality\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2.0\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e*\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNote.\u003c/span\u003e Data presented as count, median [interquartile range], or percent\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUnadjusted and adjusted model results for length of stay\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUnadjusted\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAdjusted\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDays\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRatio (95% CI)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRatio (95% CI)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eOverall\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFactor V Leiden\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e5.1\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.11 (1.03\u0026ndash;1.18)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.005\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.14 (1.09\u0026ndash;1.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge (per 10 years older)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFigure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.98 (0.97\u0026ndash;0.99)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.96 (0.96\u0026ndash;0.97)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBiological Sex\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.99 (0.98\u0026ndash;0.99)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.044\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.99 (0.98\u0026ndash;1.01)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.180\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRace\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBlack\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e5.1\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.17 (1.16\u0026ndash;1.18)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.11 (1.11\u0026ndash;1.12)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHispanic\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.8\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.09 (1.08\u0026ndash;1.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.07 (1.06\u0026ndash;1.08)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eOther\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.09 (1.07\u0026ndash;1.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.07 (1.05\u0026ndash;1.08)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWhite\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDiabetes - Uncomplicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.93 (0.92\u0026ndash;0.95)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.97 (0.96\u0026thinsp;\u0026minus;\u0026thinsp;0.78)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDiabetes - Complicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e5.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.16 (1.15\u0026ndash;1.18)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.10 (1.09\u0026ndash;1.11)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHypertension - Uncomplicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.91 (0.90\u0026ndash;0.92)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.02 (1.01\u0026ndash;1.03)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.9\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHypertension - Complicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e5.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.31 (1.29\u0026ndash;1.33)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.29 (1.28\u0026ndash;1.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHyperlipidemia\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.97 (0.96\u0026ndash;0.98)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.94 (0.94\u0026ndash;0.95)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNote\u003c/span\u003e. Ratios are interpreted relative to the reference group. For age, the reference group is 10-years younger age; for categorical variables the reference group is indicated. Ratios greater than 1 indicate longer lengths of stay relative to the reference group.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUnadjusted and adjusted model results for inflation-adjusted hospital cost\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUnadjusted\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAdjusted\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2022 US\u003cspan\u003e$\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRatio (95% CI)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRatio (95% CI)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eOverall\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15,187\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e-\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFactor V Leiden\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e17,172\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.13 (1.05\u0026ndash;1.22)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.16 (1.11\u0026ndash;1.22)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15,171\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge (per 10 years older)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFigure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.91 (0.90\u0026ndash;0.91)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.93 (0.92\u0026ndash;0.93)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBiological Sex\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15,174\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.00 (0.99\u0026ndash;1.01)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.819\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.00 (0.99\u0026ndash;1.01)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.202\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15,196\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eRace\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBlack\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15,403\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.07 (1.06\u0026ndash;1.08)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.06 (1.0-1.07)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHispanic\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e16,836\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.17 (1.16\u0026ndash;1.19)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.17 (1.16\u0026ndash;1.18)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eOther\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e17,344\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.21 (1.19\u0026ndash;1.23)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.21 (1.19\u0026ndash;1.23)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWhite\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14,340\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDiabetes - Uncomplicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13,596\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.88 (0.87\u0026ndash;0.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.92 (0.90\u0026ndash;0.93)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15,419\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDiabetes - Complicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15,256\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.01 (0.99\u0026ndash;1.02)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.493\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.99 (0.98\u0026ndash;0.99)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.020\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15,169\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHypertension - Uncomplicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14,107\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.97 (0.86\u0026ndash;0.88)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.95 (0.94\u0026ndash;0.96)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e16,231\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHypertension - Complicated\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e16,903\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.14 (1.13\u0026ndash;1.16)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.12 (1.11\u0026ndash;1.14)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14,765\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHyperlipidemia\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14,369\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.91 (0.89\u0026ndash;0.92)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.93 (0.93\u0026ndash;0.94)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15,858\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eReference\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eNote\u003c/span\u003e. Ratios are interpreted relative to the reference group. For age, the reference group is 10-years younger age; for categorical variables the reference group is indicated. Ratios greater than 1 indicate higher hospital costs relative to the reference group.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Factor V Leiden, Ischemic stroke, Stroke in young, National Inpatient Sample, Hypercoagulable state","lastPublishedDoi":"10.21203/rs.3.rs-8191559/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8191559/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe association between Factor V Leiden (FVL) and ischemic stroke in young adults remains uncertain. We evaluated inpatient FVL prevalence and hospital outcomes among young adults with ischemic stroke in the United States.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUsing the 2016\u0026ndash;2022 National Inpatient Sample, we identified hospitalizations for patients aged 18\u0026ndash;49 years with a primary diagnosis of ischemic stroke and a secondary diagnosis of FVL. FVL prevalence in stroke hospitalizations was compared with non-stroke hospitalizations. Among stroke hospitalizations, we examined discharge disposition, length of stay, and inflation-adjusted costs using survey-weighted models adjusted for demographics and comorbidities.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAmong 67.8\u0026nbsp;million hospitalizations of adults aged 18\u0026ndash;49 years, 297,905 (0.44%) were for ischemic stroke. FVL prevalence was higher in stroke than non-stroke hospitalizations (0.85% vs 0.25%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and rose modestly over time in stroke admissions (0.81% in 2016 to 0.95% in 2022). Stroke patients with FVL were younger, more often female and White, and had fewer traditional vascular risk factors. After adjustment, FVL was associated with longer length of stay (14.3% increase) and higher costs (16.5% increase), with greater effects in males and Black and Hispanic patients; discharge disposition was similar by FVL status.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFVL is more prevalent among young adults hospitalized with ischemic stroke, who did not have traditional stroke risk factors. These findings support a possible hypercoagulable mechanism in a subset of ischemic stroke patients and highlight the need for prospective studies to guide targeted screening and primary prevention strategies.\u003c/p\u003e","manuscriptTitle":"Association of Factor V Leiden and Ischemic Stroke in Young Adults: A National Inpatient Sample Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 08:22:58","doi":"10.21203/rs.3.rs-8191559/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9467167d-e5e8-48e2-ba39-6d756ba6a7dc","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-19T17:01:14+00:00","versionOfRecord":{"articleIdentity":"rs-8191559","link":"https://doi.org/10.1007/s11239-025-03233-9","journal":{"identity":"journal-of-thrombosis-and-thrombolysis","isVorOnly":false,"title":"Journal of Thrombosis and Thrombolysis"},"publishedOn":"2026-01-12 16:28:25","publishedOnDateReadable":"January 12th, 2026"},"versionCreatedAt":"2025-12-01 08:22:58","video":"","vorDoi":"10.1007/s11239-025-03233-9","vorDoiUrl":"https://doi.org/10.1007/s11239-025-03233-9","workflowStages":[]},"version":"v1","identity":"rs-8191559","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8191559","identity":"rs-8191559","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}